Radiation combined with oncolytic vaccinia virus provides pronounced antitumor efficacy and induces immune protection in an aggressive glioblastoma model

Quinn T Storozynsky; Kate C Agopsowicz; Ryan S Noyce; Amirali B Bukhari; Xuefei Han; Natalie Snyder; Brittany A Umer; Armin M Gamper; Roseline Godbout; David H Evans; Mary M Hitt

doi:10.1016/j.canlet.2023.216169

Radiation combined with oncolytic vaccinia virus provides pronounced antitumor efficacy and induces immune protection in an aggressive glioblastoma model

Cancer Lett. 2023 May 28:562:216169. doi: 10.1016/j.canlet.2023.216169. Epub 2023 Apr 14.

Authors

Affiliations

¹ Department of Oncology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada; Cancer Research Institute of Northern Alberta (CRINA), University of Alberta, Edmonton, AB, Canada.
² Department of Oncology, University of Alberta, Edmonton, AB, Canada.
³ Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada.
⁴ Department of Oncology, University of Alberta, Edmonton, AB, Canada; Cancer Research Institute of Northern Alberta (CRINA), University of Alberta, Edmonton, AB, Canada.
⁵ Department of Oncology, University of Alberta, Edmonton, AB, Canada; Department of Neurosurgery, First Hospital of Jilin University, Changchun, China.
⁶ Department of Oncology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada; Cancer Research Institute of Northern Alberta (CRINA), University of Alberta, Edmonton, AB, Canada. Electronic address: mhitt@ualberta.ca.

PMID: 37061120
DOI: 10.1016/j.canlet.2023.216169

Abstract

Glioblastoma (GB) is a malignant and immune-suppressed brain cancer that remains incurable despite the current standard of care. Radiotherapy is a mainstay of GB treatment, however invasive cancer cells outside the irradiated field and radioresistance preclude complete eradication of GB cells. Oncolytic virus therapy harnesses tumor-selective viruses to spread through and destroy tumors while stimulating antitumor immune responses, and thus has potential for use following radiotherapy. We demonstrate that oncolytic ΔF4LΔJ2R vaccinia virus (VACV) replicates in and induces cytotoxicity of irradiated brain tumor initiating cells in vitro. Importantly, a single 10 Gy dose of radiation combined with ΔF4LΔJ2R VACV produced considerably superior anticancer effects relative to either monotherapy when treating immune-competent orthotopic CT2A-luc mouse models-significantly extending survival and curing the majority of mice. Mice cured by the combination displayed significantly increased survival relative to naïve age-matched controls following intracranial tumor challenge, with some complete rejections. Further, the combination therapy was associated with an increased ratio of CD8⁺ effector T cells to regulatory T cells compared to either monotherapy. This study validates the use of radiation with an oncolytic ΔF4LΔJ2R VACV to improve treatment of this malignant brain cancer.

Keywords: Antitumor immunity; Glioblastoma; Oncolytic viruses; Radiation; Vaccinia virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Neoplasms* / therapy
Cell Line, Tumor
Glioblastoma* / therapy
Mice
Oncolytic Virotherapy*
Oncolytic Viruses* / physiology
Vaccinia virus / genetics
Xenograft Model Antitumor Assays